Involvement of oxidative stress and impaired lysosomal degradation in amiodarone‐induced schwannopathy. (7th June 2016)

• Record Type: Journal Article
• Authors: Niimi, Naoko; Yako, Hideji; Tsukamoto, Masami; Takaku, Shizuka; Yamauchi, Junji; Kawakami, Emiko; Yanagisawa, Hiroko; Watabe, Kazuhiko; Utsunomiya, Kazunori; Sango, Kazunori
• Editors: Watanabe, Masahiko
• Is Part Of: European journal of neuroscience. Volume 44:Number 1(2016:Jul.)
• Page Start: 1723
• Page End: 1733
• Publication Date: 2016-06-07
• Subjects: demyelination -- in vitro -- neurotoxicology -- peripheral neuropathy -- Schwann cells; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.13268
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Amiodarone hydrochloride (AMD), an anti‐arrhythmic agent, has been shown to cause peripheral neuropathy; however, its pathogenesis remains unknown. We examined the toxic effects of AMD on an immortalized adult rat Schwann cell line, IFRS1, and cocultures of IFRS1 cells and adult rat dorsal root ganglion neurons or nerve growth factor‐primed PC12 cells. Treatment with AMD (1, 5, and 10 μm ) induced time‐ and dose‐dependent cell death, accumulation of phospholipids and neutral lipids, upregulation of the expression of gangliosides, and oxidative stress (increased nuclear factor E2‐related factor in nuclear extracts and reduced GSH/GSSG ratios) in IFRS1 cells. It also induced the upregulation of LC3‐II and p62 expression, with phosphorylation of p62, suggesting that deficient autolysosomal degradation is involved in AMD‐induced IFRS1 cell death. Furthermore, treatment of the cocultures with AMD induced detachment of IFRS1 cells from neurite networks in a time‐ and dose‐dependent manner. These findings suggest that AMD‐induced lysosomal storage accompanied by enhanced oxidative stress and impaired lysosomal degradation in Schwann cells might be a cause of demyelination in the peripheral nervous system. Abstract : Enhanced oxidative stress and dysfunction of autophagy‐lysosome pathway in Schwann cells under exposure to amiodarone (AMD) may be a cause of demyelinating neuropathy.